Project Summary/Abstract High-content screening employs an imaging-based platform, which combines the efficacy and speed of high-throughput automation and the power of light microscopy, especially fluorescence microscopy, to simultaneously capture both functional and morphometric information from a large number of samples of cells or organisms following perturbation, such as drug treatment or genetic alteration. High content analysis permits a much more comprehensive quantitative assessment of drug and gene effects than population-based methods, because multiple kinetic and spatial readouts can be simultaneously interrogated in individual cells. This application seeks to fill the gap between a strong demand for high-content screening and the limited capability the University of Virginia can currently offer. The proposed instrument is a PerkinElmer Operetta CLS, a high-content imaging system capable of bright-field, phase-contrast, and wide-field and spinning-disc confocal fluorescence imaging. The acquisition will immediately benefit a wide range of biomedical research projects covering infectious diseases such as influenza, Ebola, cardiovascular disease, obesity, cancer, peripheral and central neurodegeneration. With the Operetta CLS, multiple parameters can be captured simultaneously for evaluation of tool or drug candidates against known targets as well as for uncovering unknown new targets in the exploration of a biological problem. Added benefit is unbiased image acquisition and powerful data analysis. The Operetta CLS is positioned to critical new research tool to facilitate our extensive basic or clinical research programs, which are attempting to understand and find treatments for human diseases.